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I also see this as more support for the "primary hypoperfusion in MS" hypothesis. The study states that the more highly perfused regions allow for remyelination. This implies that perfusion plays a direct, causal role in (de/re)myelination.

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Just wondering if anyone has measured the brain blood flow in 24 hour basis and of course to compare it with healthy controls.
I remember that night blood pressure may decrease causing effects like TIA and etc.
Just wondering

tsoft wrote:Just wondering if anyone has measured the brain blood flow in 24 hour basis and of course to compare it with healthy controls.I remember that night blood pressure may decrease causing effects like TIA and etc.Just wondering

The Haacke protocol is measuing cerebral blood flow in normals, compared to pwMS. Here's his protocol---the research will be published in the next year. He is finding slowed venous return in pwMS compared to controls. link

Here is the abstract presented by Dr. Feng, Dr. Haacke and Dr. Hubbard in Bologna. They found some interesting things....there is an imbalance between left and right sides in pwMS that he has not seen in normals. This is called "venous-arterial mismatch"...and pwMS show it more than normals. They have less blood traveling thru their IJVs.

Introduction: Recently, there has been an increased interest in the role of poor venous flow in patients with multiple sclerosis (MS) (1). The goal of this work is to understand the flow characteristics of both the major arteries and veins in the neck in an MS population. By using phase contrast MR imaging, we can evaluate the flow in a variety of locations to examine the total cardiovascular input/output to and from the brain. Inthis preliminary study, we will examine a total of 127 MS cases and present a variety of quantitative measures of the arterial and venous flow.

Methods: Institutional review board approval was obtained for the human imaging protocols performed. A total of 127 MS patients were scanned with a variety of conditions. These include relapsing remitting, secondary progressive, primary progressive, and progressive relapsing. Blood flow is measured with two dimensional PCMRI imaging on a 3T Siemens Magnetom Tim Trio with the following parameters:repetition time = 14.4ms, echo time = 4.41ms, flip angle = 25o , field of view = 256mmx256mm, acquisition matrix size = 448x448, in-plane resolution = 0.57mmx0.57mm, slice thickness = 4mm and velocity encoding (VENC) = 50cm/sec. Pulse gating was used to monitor and trigger the data acquisition. Images were acquired for a total of 25 time points during the cardiac cycle. The imaging plane was chosen tobe at the cervical 6/7 level at the lower neck and perpendicular to the internal jugular veins (IJV). Our in-house software (written in MATLAB) was used to segment vessels and compute flow. Vessel segmentation was achieved manually. In some cases the blood flow velocity exceeded our VENC and resulted in phase aliasing. This was corrected by running a simple phase unwrapping algorithm that takes into account the phase values of all the voxels throughout the cardiac cycle inside the vessel. Blood flow velocities through both veins and arteries were measured throughout the cardiac cycle. The volume flow rates at individual time points were computed by multiplying the spatial average velocity with the vessel lumen area. Then average volume flow rate was computed for the whole the cardiac cycle. The distribution of both arterial and venousblood flow in different vessels was computed after the flow was quantified. The mismatch between arterial flow and venous flow was computed via: VA mismatch (%) = (arterial flow – venous flow)/arterial flow * 100. The ratio of blood flow between the dominant vein that carries most of the venous blood and the 2nd dominant vein was calculated for each patient. Reflux blood flow for internal jugular veins was calculated by: reverse flow/forward flow * 100. Finally, the pulsatility index (PI) for both internaljugular veins was computed by: (Vmax-Vmin) / Vmean, where Vmax, Vmin and Vmean are the maximum, minimum and mean of the spatial average velocities for all the time points over the cardiac cycle.

On average, the left and right common carotid arteries carry almost the same amount of blood (6.37±1.32 mL/sec for LCCA vs. 6.32±1.59 mL/sec for RCCA). The same is true for the vertebral arteries (1.72±0.72 mL/sec vs. 1.51±0.65 mL/sec). However, the distribution of blood flow through the VAs is much more spread out than the CCAs. The blood flow through the RIJV (-6.12±2.88 mL/sec) is significantly more than theLIJV (-3.74±2.52 mL/sec). This is consistent with the findings of others. The spread between the left and right IJVs is also much more pronounced than that of the CCAs (see Fig. 1 left). Similar findings are shown for the total left and right arterial and venous flow rates. In general, arteries on both sides carry almost the same amount of blood while the right side veins carry more blood than the left side veins. Vessel crosssectionalarea is found to have more variability than the vessel flow rate, especially for the IJVs (58.4±38.2 mm 2 for LIJV and 78.4±45.6 mm2 for RIJV).

The average percentage of IJV blood flow out of the total venous flow is measured to be 71.9±19.2%. Using the categorization method in [2], out of the 127 MS patients, 42.5% were type I, 48.8% were type II and 8.7% were type III. This is significantly different from the categorization in [2] for normals. The venous-arterial mismatch is measured tobe 14.0 ±11.1%. The ratio of sub-dominant vs. dominant venous flow is 0.50±0.25. Figure 1 (right) shows the plot of subdominant flow/dominant flow ratio vs. dominant flow rate. Reflux flow was found to be 4.9±14.8% for LIJV and 1.5±6.0% for RIJV (cases with zero reflux flow were not included when calculating these measures).Finally, the pulsatility indices of the IJVs are 2.1±1.1 for LIJV and 1.9±1.0 for RIJV (cases with pulsatility index higher than 10 were not included when calculating these measures).

Discussion and Conclusions: The pronounced spread of blood flow through the left and right vertebral arteries and the left and right internal jugular veins is worth noting. It means that the blood distribution between the left and right sides can be significantly disproportionate for some patients. This could be due to various anatomical or physiological conditions. An example could be vessel stenosis on one side. Compared to the findings in [2], our measurements show that in more MS patients (48.8% for type II compared to only 22% in [2]) the internal jugular veins carry less blood out of the brain. This could be caused by CCSVI and other veins or collaterals serve as alternative pathways. It is also interesting that about 1/4 of all the MS patients have a significantly more dominant vein (meaning that the 2nd dominant vein only carries less than 20% of the blood through the dominant vein).

Thank you Cheer!
I am familiar with the work of Dr. Hackee, mostly because of your posts and your articles in the Facebook. I am looking forward to his results and believe that this will be a huge step in the right direction.
Yet my wondering was related to whether the state of the jugular veins, arteries and cerebral blood flow at all are constant state or could they be changed, eg during the night, on relapse or other circumstances.
Saying again that I'm just wondering. Maybe i'm saying just nosense...

tsoft wrote:Thank you Cheer!I am familiar with the work of Dr. Hackee, mostly because of your posts and your articles in the Facebook. I am looking forward to his results and believe that this will be a huge step in the right direction.Yet my wondering was related to whether the state of the jugular veins, arteries and cerebral blood flow at all are constant state or could they be changed, eg during the night, on relapse or other circumstances.Saying again that I'm just wondering. Maybe i'm saying just nosense...

It's not nonsense...the cardiac cycle changes while we sleep. So far, there are no 24 hour studies of CCSVI being conducted. But maybe in the future? What has been studied is sleep apnea and the affects on the cardiac cycle.

My husband used to have sleep apnea. He would wake several times in the night, gasping for air. Since his angioplasty, no more waking or gasping, only smooth, regular breathing. When we sleep, our body relies on the jugular veins to return cerebral blood to the heart. I've written much on REM sleep and oxygenation. There is probably a connecction to the return of dreams those treated for CCSVI are reporting. But more studies need to be completed...we're just getting started.
cheer

ikulo wrote:I also see this as more support for the "primary hypoperfusion in MS" hypothesis. The study states that the more highly perfused regions allow for remyelination. This implies that perfusion plays a direct, causal role in (de/re)myelination.

I don't see how myelination itself would cause increased perfusion.

I presume that oligos need oxygen & sugar just as much as every other kind of cell. I would have thought it was the other way - if you don't perfuse, you don't get myelination.

I think I may have found some important information on how phlebotomy keeps me well and how hypoperfusion in the brain is linked.
I'm now being investigated for polycythemia, as even though I now have my mild iron overload corrected my hemoglobin and hematocrit will not stay down. I started to get a return of symptoms a few weeks ago (I am due for another blood letting next week) and my hematocrit had gone up to 47.5. The article below states that when hematocrit is between .46 and .52 you get low cerebral bloodflow. Mine is currently 47.5. and I'm feeling it. I felt very well in Dec10 when it was at .43.

CEREBRAL BLOOD-FLOW IN POLYCYTHÆMIAOriginal TextD.J. Thomas , John Marshall , R.W. Ross Russell , G. Wetherley-Mein , G.H. Du Boulay , T.C. Pearson , L. Symon , E. Zilkha AbstractCerebral blood-flow (C.B.F.) has been measured in 16 patients with polycythæmia of differing severity. The mean C.B.F. was 37.9 ml/100 g/min, which is significantly below the normal level of 69.1 (S.D. 9.3) ml/100 g/min (p<0.001). C.B.F. measurement was repeated after venesection in 15 of the patients. Lowering the hæmatocrit from a mean of 0.536 to a mean of 0.455 was associated with a 73% increase in mean C.B.F. (P<0.001) and a 30% reduction in whole-blood viscosity. Low C.B.F. was found at hæmatocrit levels between 0.46 and 0.52. Hæmatocrit levels that are currently considered acceptable in the management of polycythæmia may therefore be too high.

Then I found this research which shows that demylenation of the CNS happens in Polycythemia. I had a bout of Chorea in January 201010 days after my first phlebotomy.

Polycythemia and chorea.Marvi MM, Lew MF.AbstractPolycythemia vera is a sporadic myeloproliferative disorder of increased red blood cell mass affecting multiple organ systems. Associated thrombosis, hemorrhaging, and hyperviscosity commonly result in neurological manifestations, sometimes in the form of chorea and ballism. Resultant choreiform movements have been mainly described as generalized with orofaciolingual and appendicular muscle involvement, hypotonia, and hyporeflexia. Chorea has also been uncommonly reported as arising from secondary causes of polycythemia; however, the underlying pathophysiology has not been clearly elucidated. Proposed mechanisms for basal ganglia dysfunction include hypoperfusion due to venous stasis, receptor hypersensitivity in a setting of reduced catecholamine levels, and altered platelet dopamine metabolism. Magnetic resonance imaging and single-photon emission computed tomography perfusion studies have failed to reveal an anatomical or physiological basis for polycythemia vera-associated chorea, yet rare pathological examinations of deceased patients have shown signs of cerebral venous thrombosis and perivenous demyelination. Administration of neuroleptics may suppress abnormal choreiform movement; however, effective management of polycythemia vera requires serial venesections in conjunction with chemotherapy. Appropriate treatment may prolong survival to more than 10 years, although chorea may spontaneously remit, re-emerge with resurgence of disease, or continue indefinitely despite maintenance therapy.

To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.

RESULTS:

Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified.

The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.

CONCLUSION:

It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

from the text of the article:

Restoration of blood flow following removal of the stimulus would produce a rapid clinical improvement.

How about that... And, if this article has already been posted, ah well, this is a reminder.

Wanted to bump this thread for Dr. Tucker and others relatively new to the CCSVI forum.

The Hubbard Foundation will be beginning perfusion studies in pwCCSVI and in normals. Start at the beginning of this thread to read Shayk's wonderful first post and the ongoing research on slowed perfusion in MS.cheer

Hypo or slowed perfusion is a problem which appears to be reversed following balloon venoplasty. This is a great reason for treating CCSVI syndrome with balloon venoplasty. The thread gives lots of interesting info on how this is linked to MS but the is not currently sufficient data to demostrate the link to MS.

Animal studies have revealed the molecular cascades that are initiated with hypoxia/ischemia in the cells forming the neurovascular unit and that contribute to cell death. Matrix metalloproteinases cause reversible degradation of tight junction proteins early after the onset of ischemia, and a delayed secondary opening during a neuroinflammatory response occurring from 24 to 72 hours after. Cyclooxygenases are important in the delayed opening as the neuroinflammatory response progresses. An early opening of the BBB within the 3-hour therapeutic window for tissue-type plasminogen activator can allow it to enter the brain and increase the risk of hemorrhage. Chronic hypoxic hypoperfusion opens the BBB, which contributes to the cognitive changes seen with lacunar strokes and white matter injury in subcortical ischemic vascular disease. This review will describe the molecular and cellular events associated with BBB disruption and potential therapies directed toward restoring the integrity of the neurovascular unit.

So, for dummies (like me): hypoxia kills (cells, tissue, people) and hypoperfusion is slowed blood transit -- tapped-out blood with low or no oxygen left, that hangs around too long. My guess is there could be varying degrees of this, from A) low level hypoxia caused by more oxygen being already gone by the time it reaches any particular area, because upstream perfusion lowered the level too far, or too much reaction time and too many oxidants, to B) higher level hypoxia caused by even slower blood transit, with the same effects, plus the 'cascade' from all the oxidants and hypoxia itself, causing actual cell death, or apoptosis, which is programmed death (part of the 'cascade'?).

You can see how this happens, when a stroke blows a blood vessel. My first 'sudden' attack (I woke up with it one morning) was before I was diagnosed. I thought, because I have stroke in my family, that I had had one. I found out what it was, much later, but I thought it had been a stroke for a long time. In fact I have never understood the suddenness of my attacks, being apparent first thing in the morning, except that perhaps there is jugular or other circulatory involvement, something affected by my posture being different from day to night.

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